Studies are proposed to analyze the apoptosis signaling pathways in dendritic cells and the effects of defective dendritic cell apoptosis on self tolerance. To study dendritic cell apoptosis and immune tolerance, experiments are proposed to: 1. To characterize the death pathways in dendritic cells: 1a. define the roles of death receptors in dendritic cell apoptosis. lb. Study the signaling molecules in dendritic cell death pathways. 2. To study how maturation of dendritic cells regulates apoptosis. 3. To determine the contribution of defective dendritic cell apoptosis to autoimmunity: 3a. Study dendritic cell deletion in an adoptive transfer model using dendritic cells transduced with apoptotic inhibitors. 3b. Study autoimmune responses in transgenic mice expressing apoptotic inhibitors in dendritic cells. Dendritic cells have emerged as a cell type critical for initiating and regulating immune responses. The proposed study may provide insights into the roles of dendritic cell apoptosis in self tolerance and autoimmunity.